Chemical modification endows heparin with low anticoagulant and high antineoplastic ac-tivities
10.3969/j.issn.1673-4254.2015.01.08
- VernacularTitle:化学修饰赋予肝素低抗凝血活性和高抗肿瘤活性
- Author:
Ying LIANG
1
;
Libiao LI
;
Pei ZHANG
;
Chengzhu WU
;
Surong ZHAO
;
Qianwen ZHANG
;
Hao LIU
;
Zhiwen JIANG
Author Information
1. 安徽省生化药物工程技术研究中心
- Keywords:
heparin;
chemical modification;
antiproliferative activity;
anti-invasion activity;
anticoagulant activity
- From:
Journal of Southern Medical University
2015;(1):40-46
- CountryChina
- Language:Chinese
-
Abstract:
Objective To evaluate the anticoagulant and antineoplastic activities of chemically modified low-molecular-weight heparin (LMWH). Methods LMWH obtained by splitting unfractionated heparin (UFH) with sodium periodate oxidation and sodium borohydride reduction was subjected to acetylation catalyzed by DCC and DMAP to produce acetylated LMWH (ALMWH). The anticoagulant activity of ALMWH was determined in mice, and its antiproliferative and anti-invasion activities was assessed in human breast cancer cells MDA-MB-231 and MFC-7. Results The anticoagulant activity of LMWH was decreased significantly after acetylation. The concentrations of commercial LMWH* and ALMWH for doubling the coagulation time (CT) were 33.04 μmol/L and 223.56 μmol/L, respectively, and the IC50 of ALMWH for doubling CT was 6 times of that of LMWH*. ALMWH and LMWH at 0.1, 0.3, 0.9, 2.7 and 8.1 mmol/L both significantly inhibited the proliferation of MDA-MB-231 and MCF-7 cells in a concentration-dependent manner, but ALMWH produced stronger inhibitory effects. The IC50 of LMWH and ALMWH for inhibiting cell proliferation was 3168.4 μmol/L and 152.6 μmol/L in MCF-7 cells, and 12299.6 μmol/L and 22.2 μmol/L in MDA-MB-231 cells, respectively. ALMWH and LMWH all markedly suppressed the invasion of MDA-MB-231 cells with comparable effects. Conclusion Chemical modification of structure can endow LMWH with a low anticoagulant and high antiproliferative activities.
